rs6696657

chr1-210344738-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018194.6(HHAT):c.-43-4195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,922 control chromosomes in the GnomAD database, including 13,925 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13925 hom., cov: 31)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

Genes affected

HHAT (HGNC:18270): (hedgehog acyltransferase) 'Skinny hedgehog' (SKI1) encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of 'hedgehog' (see MIM 600725).[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HHAT	NM_018194.6	c.-43-4195C>T		intron_variant		ENST00000261458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HHAT	ENST00000261458.8	c.-43-4195C>T		intron_variant		2	NM_018194.6	P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63998 AN: 151804 Hom.: 13899 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.420

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.422 AC: 64080 AN: 151922 Hom.: 13925 Cov.: 31 AF XY: 0.420 AC XY: 31203 AN XY: 74228

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.419

Alfa AF: 0.413 Hom.: 21977

Bravo AF: 0.420

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.080
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6696657; hg19: chr1-210518082; COSMIC: COSV54809065;